Evaluation of the protective effect of coenzyme Q10 against x-ray irradiation-induced ovarian injury.

AIM: This study focused on the anti-oxidant and anti-apoptotic effects of CoQ10 in ovaries exposed to pelvic radiation. METHODS: Thirty-two female rats were randomly assigned into four groups. Group I (control group), Group II: Only 2 Gy pelvic x-ray irradiation (IR) was administered as a single fractioned dose. Group III: 30 mg/kg CoQ10 was administered by oral gavage +2 Gy pelvic IR. Group IV: 150 mg/kg CoQ10 was administered by oral gavage +2 Gy pelvic IR. CoQ10 treatment was started 7 days before pelvic IR and completed 7 days later. The rats in Group III and IV were treated with CoQ10 for a total of 14 days. RESULTS: Histopathological analysis showed severe damage to the ovarian tissue in the radiation group, while both doses of CoQ10 showed normal histological structure. Likewise, while there was a high level of staining in the IR group for necrosis and apoptosis, the CoQ10 treated ones were like the control group. Tissue Malondialdehyde (MDA) levels were like the control group in the low-dose CoQ10 group, while the MDA levels of the high dose CoQ10 group were similar to the radiation group. CONCLUSION: Usage of low-dose CoQ10 has a radioprotective effect on radiation-induced ovarian damage. Although the use of high doses is morphologically radioprotective, no antioxidative effect was observed in the biochemical evaluation.

Effects of Simulation on Nursing students' Knowledge and Learning Related to Measles Vaccine and Vaccine Hesitancy: A Mixed Method Study.

Vaccine hesitancy is a persistent, global public health concern that community health nurses are well-positioned to manage. Simulations involving standardized patients are effective experiential learning on managing vaccine hesitancy for other allied health disciplines. A pretest-posttest design, with a mixed-methods, one-group, quasi-experimental approach, was used to examine the effectiveness of a simulation on nursing students' knowledge of measles, mumps, and rubella vaccine hesitancy, as well as their attitudes toward the intervention. The study was completed with 61 participants. After participation in the simulation, pretest/posttest data showed a mean increase in participants' knowledge of the measles, mumps, and rubella vaccine. There was a significant improvement in the test scores from 62.62 ± 14.82 to 69.50 ± 15.75; z = -3, 897 (1-17 days) (p = 0.001). A postintervention questionnaire revealed participants most appreciated the direct interaction with a live person, the opportunity to observe classmates' performance and share feedback, multistage structure, and safety. Drawbacks included stress from being observed by peers, time constraints, and the necessity of sharing the nursing role with a partner during the scenario. Another drawback is the simulation's inability to effectively prepare participants for hesitancy in clinical settings as they needed to assess natural clinical settings. Simulations incorporating vaccine hesitancy education and standardized patients can effectively prepare nursing students for situations related to vaccine hesitancy in community clinical settings.

The protective effects of ginseng on x-irradiation-induced intestinal damage in rats.

Although radiotherapy is widely employed in the treatment of various malignancies in oncology patients, its use is limited by the toxic effects it causes in surrounding tissues, including the gastrointestinal system. Korean Red Ginseng (KRG) is a traditional drug reported to possess antioxidant and restorative properties in various studies. The purpose of the present study was to investigate the protective effects of KRG against radiation-associated small intestinal damage. Twenty-four male Sprague Dawley rats were randomly assigned into three groups. No procedure was performed on Group 1 (control) during the experiment, while Group 2 (x-irradiation) was exposed to radiation only. Group 3 (x-irradiation + ginseng) received ginseng via the intraperitoneal route for a week prior to x-irradiation. The rats were killed 24 h after radiation. Small intestinal tissues were evaluated using histochemical and biochemical methods. An increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH) were observed in the x-irradiation group compared to the control group. KRG caused a decrease in MDA and caspase-3 activity and an increase in GSH. Our findings show that it can prevent damage and apoptotic cell death caused by x-irradiation in intestinal tissue and can therefore play a protective role against intestinal injury in patients receiving radiotherapy.

Determining T and B Cell development by TREC/KREC analysis in primary immunodeficiency patients and healthy controls.

T cell receptor excision circles (TRECs) and kappa-deleting excision circles (KRECs) are DNA fragments potentially indicative of T and B cell development, respectively. Recent thymic emigrants (RTEs) are a subset of peripheral cells that may also represent thymic function. Here, we investigated TREC/KREC copy numbers by quantitative real-time PCR in the peripheral blood of patients with primary immunodeficiencies (PIDs, n = 145) and that of healthy controls (HCs, n = 86) and assessed the correlation between RTEs and TREC copy numbers. We found that TREC copy numbers were significantly lower in children and adults with PIDs (P < .0001 and P < .002, respectively) as compared with their respective age-matched HCs. A moderate correlation was observed between TREC copies and RTE numbers among children with PID (r = .5114, P < .01), whereas no significant correlation was detected between RTE values and TREC content in the HCs (r = .0205, P = .9208). Additionally, we determined TREC and KREC copy numbers in DNA isolated from the Guthrie cards of 200 newborns and showed that this method is applicable to DNA isolated from both peripheral blood samples and dried blood spots, with the two sample types showing comparable TREC and KREC values. We further showed that RTE values are not always reliable markers of T cell output. Although additional confirmatory studies with larger cohorts are needed, our results provide thresholds for TREC/KREC copy numbers for different age groups.

The cardioprotective effects of perindopril in a model of polymicrobial sepsis: The role of radical oxygen species and the inflammation pathway.

Mortality rates associated with myocardial dysfunction due to sepsis and septic shock are generally high across the world. The present study focused on the antioxidant and anti-inflammatory effects of perindopril (PER) for the purpose of preventing the adverse effects of sepsis on the myocardium and developing new alternatives in treatment. The control group received only saline solution via the oral route for 4 days. The second group underwent cecal ligation puncture (CLP), and the third underwent CLP and received PER (2 mg/kg). Rats in the third group received 2 mg/kg PER per oral (p.o.) from 4 days before induction of sepsis. Thiobarbituric acid reactive species (TBARS), total thiol (-SH), interleukin-1 beta (IL-1ß), IL-6, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κB/p65) levels increased in the CLP groups. In contrast, PER (2 mg/kg) decreased the levels of biochemical parameters other than total-SH and decreased 8-OHdG, NF-κB/p65 immunopositivity in rat heart tissues. The data from this study show that impairment of the oxidant/antioxidant balance and inflammatory cytokine levels in favor of inflammation in heart tissue under septic conditions results in severe tissue damage. PER administration before sepsis was shown to exhibit antioxidant and anti-inflammatory properties by reducing these effects. This in turn increased the importance of PER as new evidence of its protective effects in heart tissue.

Tracing Size and Surface Chemistry-Dependent Endosomal Uptake of Gold Nanoparticles Using Surface-Enhanced Raman Scattering.

Surface-enhanced Raman scattering (SERS)-based single-cell analysis is an emerging approach to obtain molecular level information from molecular dynamics in a living cell. In this study, endosomal biochemical dynamics was investigated based on size and surface chemistry-dependent uptake of gold nanoparticles (AuNPs) on single cells over time using SERS. MDA-MB-231 breast cancer cells were exposed to 13 and 50 nm AuNPs and their polyadenine oligonucleotide-modified forms by controlling the order and combination of AuNPs. The average spectra obtained from 20 single cells were analyzed to study the nature of the biochemical species or processes taking place on the AuNP surfaces. The spectral changes, especially from proteins and lipids of endosomal vesicles, were observed depending on the size, surface chemistry, and combination as well as the duration of the AuNP treatment. The results demonstrate that SERS spectra are sensitive to trace biochemical changes not only the size, surface chemistry, and aggregation status of AuNPs but also the endosomal maturation steps over time, which can be simple and fast way for understanding the AuNP behavior in single cell and useful for the assisting and controlling of AuNP-based gene or drug delivery applications.

Importance of endothelial dysfunction biomarkers in patients with Crimean-Congo hemorrhagic fever.

The pathogenesis of the Crimean-Congo hemorrhagic fever (CCHF) and the cause of the hemorrhage are not yet fully understood. However, the endothelium plays a key role in the pathogenesis. The purpose of this study was to investigate endothelial dysfunction markers (asymmetrical dimethyl arginine [ADMA], endothelin 1[ET-1], thrombomodulin [TM], von Willebrand factor [vWf], and intercellular adhesion molecule [ICAM-1]) in serum in patients with CCHF and their associations with hemorrhage. Seventy-three patients with CCHF were included in the study. All patients' endothelial dysfunction markers were studied using routine biochemical and hematological tests. The data obtained were then subjected to statistical analysis. Statistically significant differences were determined between the patients and healthy control groups at time of presentation to hospital in terms of ADMA (P < 0.001), ET-1 (P < 0.001), TM (P = 0.039), vWf (P < 0.001), and ICAM-1 (P < 0.001) levels. Only the differences in TM and vWf were significant between the hemorrhagic and non-hemorrhagic groups (P < 0.05). Both serum ADMA and TM levels were significantly higher in the hemorrhage and non-hemorrhage CCHF groups on the 5th day compared to the 1st day (P < 0.05). Levels of endothelial dysfunction markers in CCHF vary in proportion to the damage occurring in the endothelium. ADMA and TM levels were lower in periods with mild endothelial injury. They were increased in line with severity endothelial injury. They may be an early marker in showing hemorrhage. Elevation in ADMA levels and low nitric oxide levels lead to endothelial injury and hemorrhage. Soluble TM that entered the circulation in line with the increased endothelial injury in hemorrhagic patients has been compromised the coagulation cascade.

The prognostic significance of serum troponin T levels in Crimean-Congo hemorrhagic fever patients.

Crimean-Congo Hemorrhagic Fever (CCHF) is a disease transmitted by the Crimean-Congo hemorrhagic fever virus (CCHFV), characterized by severe fever and hemorrhage and with a reported fatality level of 3-30%. Cerebral hemorrhage, gastrointestinal hemorrhage, severe anemia, shock, myocardial infarction, pulmonary edema, and pleural effusion may be seen as causes of death. Cardiac troponin T (cTn-T) is a biochemical marker with high sensitivity and specificity in myocardial injury. The purpose of this study was to determine the prognostic significance of serum troponin T levels in CCHF patients. Patients hospitalized with a diagnosis of CCHF and whose serum cTn-T was investigated were examined retrospectively. Patients were divided into two groups on the basis of presence or absence of hemorrhage. Data were subjected to statistical analysis. One hundred thirty-five CCHF patients and 72 control subjects were included. Hemorrhage was present in 48 (35.6%) patients. Mean serum cTn-T level was 17.3 ± 28.0 ng/L in the patients with hemorrhage, 9.98 ± 5.97 ng/L in the non-hemorrhage patients (P = 0.001) and 6.6P = 2.6 ng/L in the control samples (P < 0.001). At a cTn-T level cut-off point of 9 ng/L, area under the ROC curve was 0.797 (95%CI: 0.730-0.854), sensitivity 83.0%, specificity 87.5%, PPD 95.7%, and NPV 60.3%. At logistic regression analysis, a rise in cTn-T level above 14 ng/L increased the probability of hemorrhage in CCHF patients approximately threefold. An increased troponin T level may be a prognostic risk factor for hemorrhage in CCHF patients. This marker should therefore be borne in mind in determining treatment strategy in these patients. J. Med. Virol. 89:408-412, 2017. © 2015 Wiley Periodicals, Inc.

The prognostic significance of serum TGF-ß1 levels in patients with Crimean-Congo hemorrhagic fever.

Crimean-Congo Hemorrhagic Fever (CCHF) may exhibit a mild clinical course or a severe profile like mortal bleeding. The pathogenesis of the illness and reason of bleeding are unclear. However, endothelial injury is a key factor in the pathogenesis of the illness. Transforming growth factor beta (TGF-ß) is one of the materials involved in repairing injured endothelium. This is a significant polypeptide released in pretty much all cells and important for the regulation of cellular events, epithelium formation, inflammation, blood coagulation, and collagen synthesis. This study aimed to determine the prognostic significance of serum TGF-ß1 levels in CCHF patients. We examined 120 patients hospitalized with CCHF diagnosis and their serum TGF-ß1 was investigated, retrospectively. Patients were put into two groups according to the existence of hemorrhage. Forty-four (36.7%) patients had hemorrhage. TGF-ß1 levels in patients with bleeding were 5.2 ± 1.8, and 7.1 ± 2.2 for non-bleeding (P < 0.0001). When ROC analysis was performed in patients with CCHF alone in order to identify patients with bleeding, at a TGF-ß1 cut-off point of 4.9, AUC was 0.762 (0.675-0.835), sensitivity 59.1%, specificity 85.5%, PPV 70.3%, and NPV 78.3%. We summarize that TGF-ß1 level and endothelial dysfunction can be related. A decreased TGF-ß1 level is a likely prognostic and diagnostic factor for bleeding in CCHF patients. Therefore, this marker should be considered in the treatment strategy for these patients. J. Med. Virol. 89:413-416, 2017. © 2016 Wiley Periodicals, Inc.

Prognostic impact of platelet distribution width in patients with Crimean-Congo hemorrhagic fever.

Platelet distribution width (PDW) is a readily available blood test involving calculations performed by automated blood analyzers. Crimean-Congo hemorrhagic fever (CCHF) may exhibit a severe profile with fatal hemorrhaging or else present with a mild clinical process. The purpose of our study was to investigate the importance of PDW in CCHF patients and its clinical prognostic value. This study was conducted with patients with CCHF. Patients were divided into two groups on the basis of presence or absence of bleeding. Demographic characteristics, clinical findings, PDW, and other laboratory tests were recorded onto forms. A total of 423 patients were included. Hemorrhaging was observed in 27.9% during hospitalization. PDW on the first day of hospitalization was 17.2 ± 0.9% in the hemorrhagic patients and 17.1 ± 0.6% in the cases without hemorrhage (P = 0.290). On the third day of hospitalization, PDW was 17.6 ± 0.8% in the hemorrhagic patients and 17.0 ± 0.7% in the cases without hemorrhage (P < 0.001). At a third-day PDW level cut-off point of 17.1%, AUROC was 0.677, sensitivity 65.5%, specificity 54.6%, PPV 35.5%, and NPV 80.6%. A one-unit raise in third day PDW stepped up the probability of bleeding in patients with CCHF 3.45-fold at logistic regression analysis. This study shows that PDW is a parameter that may be used to determine disease severity. This parameter may be at least as useful as platelet count in helping clinicians identify severe cases. Early identification of cases with a severe course will make it possible to provide early planning of modalities such as intensive care support. J. Med. Virol. 88:1862-1866, 2016. © 2016 Wiley Periodicals, Inc.

Importance of serum adipokine and ghrelin levels in patients with Crimean-Congo hemorrhagic fever.

Crimean-Congo Hemorrhagic Fever (CCHF) may present with a mild clinical course or else exhibit a severe profile with potentially fatal hemorrhaging. The pathogenesis of the disease has not yet been well described. Cytokines have recently been investigated in order to explain the pathogenesis. The latest reports show that adipokines are powerful inflammation modulators. This study investigated the effect of adipokines (resistin, leptin, and adiponectin) and ghrelin on disease severity in CCHF patients by testing their serum levels. This retrospective study was conducted with patients with CCHF hospitalized at the Karadeniz Technical University, Medical Faculty in Turkey. Patients were divided into severe and non-severe groups. Serum adipokine levels of patients with CCHF were measured using enzyme-linked immunosorbent assay (ELISA). Fifty-three patients with confirmed CCHF were investigated. Twenty-five (47.2%) of these patients constituted the severe group. Serum resistin levels in the severe and non-severe groups were 108.9 ± 24.7 ng/ml and 77.5 ± 27.7 ng/ml (P < 0.001), leptin levels 15.5 ± 9.8 and 11.2 ± 5.1 ng/ml (P = 0.074), adiponectin levels 26.8 ± 18.9 and 27.4 ± 16.3 ng/ml (P = 0.903) and ghrelin levels 57.1 ± 48.7 and 200.9 ± 182.7 ng/ml (P = 0.001), all respectively. This study confirms that significant changes in serum levels of resistin and ghrelin take place in severe CCHF.

Outcome of the Modified St. Jude Total XV Protocol in Turkish Children with Newly Diagnosed Acute Lymphoblastic Leukemia: A Single-Center Retrospective Analysis

Objective: The prognostic factors and outcomes of Turkish children with newly diagnosed acute lymphoblastic leukemia (ALL), treated with the Modified St. Jude Total XV Protocol, which was adjusted by adding high-dose methylprednisolone (HDMP) before induction in the original protocol, were assessed in this study. Materials and Methods: The Modified St. Jude Total XV Protocol was administered to 183 newly diagnosed ALL patients, aged 1-18 years, between 1 January 2008 and 30 January 2016. HDMP was applied at doses of either 10 mg/kg/day (Group A) or 20 mg/kg/day (Group B) for 7 days before induction and then tapered over the next 7 days to 5 or 10 mg/kg/day, and continued at 2 mg/kg/day for 2 weeks during the induction phase. Absolute blast count (ABC) in peripheral blood and minimal residual disease (MRD) in bone marrow were assessed at the end of the initial 7-day HDMP treatment. MRD in the bone marrow was evaluated on day 15 and at the end of the induction period. The follow-up for these patients ended on 15 July 2019. Results: The 5-year event-free (EFS) and overall survival (OS) rates for all patients were 85.6±2.6% and 89.2±2.3%, respectively. The rate of good response to steroids (defined as ABC in peripheral blood of less than 1000/mm3 on day 7) was 88% and 97% of children achieved complete remission after induction. The survival rate and infection frequency did not show statistically significant differences between Group A and B. EFS and OS correlated with initial leukocyte count, age of 10-18 years at diagnosis, CD20 positivity at diagnosis, and gram-negative bacterial infection during remission induction. Conclusion: The remarkable response rates on days 7 and 15, along with the promising EFS and OS results in childhood ALL patients treated with the Modified St. Jude Total XV Protocol, highlight the early and substantial response effect of HDMP. At the onset of induction, short-term HDMP can be initiated, preferably at 10 mg/kg/day for the first 7 days, to minimize potential side effects.

Investigation of the effects of white tea on liver fibrosis: An experimental animal model.

Liver fibrosis is a common, progressive disease that affects millions of patients worldwide. In this study, it was aimed at investigating the effect of white tea on liver fibrosis in an in-vivo environment by creating an experimental liver fibrosis model on rats. In this study, an experimental liver fibrosis model was created with carbon tetrachloride (CCl4) in Sprague-Dawley rats to investigate the effect of white tea on liver fibrosis. Rats are treated with CCl4 (1 mL/kg) to constitute the liver fibrosis model. White tea was given ad libitum with drinking water. As a result of the study, liver tissue hydroxyproline levels were found to be significantly lower (p = .001) in the white tea group. Histopathologically, it was found that the liver tissue histopathological damage score (LHDS) and fibrosis scoring were significantly lower (p < .001) in the white tea group. However, although it was not statistically significant in the group given white tea, compared with the fibrosis group, it was found that the malondialdehyde (MDA) level in the liver tissues was lower, the glutathione (GSH) level was higher, and the serum alanine aminotransferase (ALT) levels were lower. The study explained the effect of white tea on liver fibrosis and suggested that white tea might be beneficial in reducing the progression of liver fibrosis.

The Effects of Active Warming on Core Body Temperature and Thermal Comfort in Patients After Transurethral Resection of the Prostate: A Randomized Clinical Trial.

Prevention and treatment of hypothermia by active warming in perioperative period care is recommended but scientific evidence of its effectiveness in a clinical setting is scarce. The purpose of this study was to determine the effects of warmed intravenous fluids (WIVF) on the core body temperature and the patients' thermal comfort. Baseline data of 105 male patients undergoing TUR-P surgery and bladder irrigation were analyzed. The experimental group was warmed using active WIVF, and the control group's routine care was conducted using a cotton blanket. Body temperature was higher in patients in the experimental group than those in the control group. Repeated measures Manova revealed significantly different core temperature changes between groups (F = 34.446, p = .001). The thermal comfort scores were also higher in the experimental group than in the control group (x2 = 203.552, p = .001). The findings indicated that WIVF can enhance body temperature and improve the thermal comfort of patients.

Comparison of cord blood and 6-month-old vitamin D levels of healthy term infants supplemented with 400 IU/day dose of vitamin D.

OBJECTIVES: To determine the prevalence and risk factors of vitamin D deficiency in pregnant women and their infants at birth (cord blood) and at six months of age in Turkey, as well as to assess the compliance rates of families with vitamin D supplementation. METHODS: Serum 25-hydroxyvitamin D [25(OH)D] level was measured of the mothers before delivery and of the infants both at birth (cord blood) and at six months of age. Infants who received and did not take regular vitamin D supplements were compared in terms of 25(OH) levels. Independent risk factors were determined by multiple logistic regression analysis. RESULTS: The study included a total of 140 pregnant women and their infants. Vitamin D deficiency was found in 95.7% of the mothers. The prevalence of vitamin D deficiency was 87.1% in infants at birth but decreased to 5.8% at sixth month. 65.7% of infants received vitamin D supplements regularly. Despite regular vitamin D use, it was determined that 2.2% of the infants in the supplementation compliant group had vitamin D deficiency. Maternal age, maternal education level, and the number of siblings were determined to be determining factors on infants' 25(OH)D levels at six months (p < 0.05). CONCLUSIONS: In Turkey, vitamin D deficiency still exists in both pregnant women and infants. Healthcare professionals and the public need to be more educated about the importance of regular supplementation. Serum 25(OH)D levels of infants should be tested periodically and personalized vitamin D supplementation planning is required based on test results.

Celastrol restricts experimental periodontitis related alveolar bone loss by suppressing inflammatory cytokine response.

Introduction: Periodontitis is a common chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. The host defense mechanisms are responsible for inflamatuar and destructive reactions in periodontitis. Celastrol is one of the most promising components of the plant in Eastern and Southern China that has a long history of use in traditional medicine for the treatment of inflammatory conditions. Aim: The aim of this animal study was to inspect the preventive or restrictive effects of celastrol on periodontitis-related inflammatory host response and alveolar bone loss. Methods: 24 male Sprague Dawley rats were randomly assigned into 3 groups: control, experimental periodontitis (Ep), and experimental periodontitis-celastrol (Ep-Cel). Periodontitis was induced by placing ligatures sub-paramarginally around the mandibular first molars of the rats in the Ep and Ep-Cel groups and maintaining the ligatures for 15 days. For 14 days following the ligature placement, celastrol administration (1 mg/kg BW day) for the Ep-Cel group and vehicle injection for the control and Ep groups was carried out. At the end of the experiment, mandibula and gingiva samples were obtained after the euthanasia. Alveolar bone loss was measured on serial histological slices; Tumor Necrosis Factor-α and Interleukin-1ß levels were measured on gingiva samples by ELISA. Results: Systemic celastrol administration significantly restricted the alveolar bone loss that was higher in rats with periodontitis. (p < 0.05) Tumor Necrosis Factor-α and Interleukin-1ß levels that were high in the gingiva of the rats with periodontitis were found significantly lower in rats administered celastrol. (p < 0.05). Conclusion: Celastrol restricted periodontitis-related alveolar bone loss by suppressing the inflammatory response.

Eltrombopag for the Treatment of Poor Graft Function Following Haematopoietic Cell Transplantation: Real-Life Data

Background: Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. Aims: To present our centre's experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Study Design: Retrospective cross-sectional study. Methods: Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. Results: The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x109/l (1-23), which increased to 41x109/l (6-150). The median platelet count increment was 29.5x109/l (p = 0.001). The pre-treatment median neutrophil count was 1.19x109/l (0.39-5.1), which increased to 2.35 x109/l (0.1-5.33) (p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl (p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. Conclusion: The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Surface-enhanced infrared absorption spectroscopy for microorganisms discrimination on silver nanoparticle substrates.

Extracting molecular level label-free information from complex biological processes for a range of purposes including disease diagnosis and microbial identification and discrimination is always a challenging task. This is mostly due to lack of a technique providing rich molecular information with a high spatial and temporal resolution properties. Two surface-enhanced vibrational spectroscopic (SEVS) techniques, surface-enhanced Raman scattering (SERS) and surface-enhanced infrared absorption spectroscopy (SEIRAS), are recently attracting considerable attention to study biosystems at an interface since they can satisfy these requirements to a certain level by providing rich intrinsic molecular information from molecules and molecular systems in a close proximity of nanostructured noble metal surfaces. In this study, these two surface-enhanced vibrational spectroscopic techniques are comparatively evaluated for the discrimination and identification of Candida albicans (C. albicans), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by paying attention to the source of the observed spectral pattern. The citrate-reduced colloidal silver nanoparticles (AgNPs) were used as substrates. The results show that the SEIRAS provides very rich molecular information about the biomolecular species adsorbed onto AgNPs similar to the case of SERS. The discrimination power of SEIRAS is much improved compared to FTIR demonstrated by PCA analysis. This study suggests that SEIRAS can be a potential technique for microbial analysis.

Pharmaceutical applications of a nanospectroscopic technique: Surface-enhanced Raman spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) is a very sensitive technique offering unique opportunities for detection and identification of molecules and molecular structures at extremely low concentrations even in complex sample matrixes. Since a nanostructured noble metal surface is required for the enhancement of Raman scattering, the acquired spectral information naturally originates from nanometer size domains making it a nanospectroscopic technique by breaking the diffraction limit of light. In this review, first Raman spectroscopy, its comparison to other related techniques, its modes and instrumentation are briefly introduced. Then, the SERS mechanism, substrates and the parameters influencing a SERS experiment are discussed. Finally, its applications in pharmaceuticals including drug discovery, drug metabolism, multifunctional chemo-photothermal-therapy-delivery-release-imaging, drug stability and drug/metabolite detection in complex biological samples are summarized and elaborated.

Somatic hypermutation defects in two adult hyper immunoglobulin M patients.

Hyper immunoglobulin M (HIGM) syndrome is a rare disorder of the immune system with impaired antibody functions. The clinical picture of the patients varies according to the underlying genetic variation. In this study, we identified two novel variants in AID and UNG genes, which are associated with autosomal recessive type HIGM, by targeted next-generation sequencing (NGS) panel. A biallelic 11 base pair deletion (c.278_288delATGTGGCCGAC) in the coding sequence of activation-induced cytidine deaminase (AID) gene was identified in a 36-year-old patient. Biallelic two base pair insertion in exon 7 of uracil nucleoside glycosylase (UNG) gene (c.924_925insGG) was identified in a 40-year-old patient. Both variants were confirmed by Sanger sequencing. HIGM, like many of the other primary immunodeficiencies, is a rare and difficult-to-diagnose entity with heterogeneous clinical phenotypes. It should be suspected in patients with a history of early-onset recurrent respiratory infections, enlarged lymph nodes, and autoimmune disorders. There might be a delay in diagnosis until adulthood especially in subtle cases or if HIGM is not included in the differential diagnosis due lacking of awareness. In this regard, genetic testing with NGS-based diagnostic panels provide a rapid and reasonable tool for the molecular diagnosis of patients with immunodeficiencies and hence, decrease the time to diagnose and prevent infection-related complications associated with increased morbidity and mortality.